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Last literature review version 17.3: September 2009 | This topic last updated:
June 3, 2009 (More)
The definition, epidemiology, and risk factors of sepsis and SIRS are reviewed here.
The pathophysiology and treatment are discussed separately. ( See "Pathophysiology
of sepsis" and see "Management of severe sepsis and septic shock in adults" ).
Sepsis — In sepsis, the clinical signs that define SIRS are present and are due to
either a culture-proven infection or an infection identified by visual inspection ( show
table 1) [1] . The severity of sepsis is graded according to the associated organ
dysfunction and hemodynamic compromise.
The 1992 ACCP/SCCM definitions were revisited in 2001 during an International Sepsis
Definitions Conference convened by the SCCM, European Society of Intensive Care
Medicine (ESICM), ACCP, American Thoracic Society (ATS), and Surgical Infection
Society (SIS) [ 3] . A practical modification of the definitions has since been published,
including exact hemodynamic definitions of septic shock [ 5] . The definitions described
below are based upon these resources.
Severe sepsis — Severe sepsis exists if there is sepsis plus at least one of the
following signs of organ hypoperfusion or dysfunction ( show table 1 ):
Septic shock — Septic shock exists if there is severe sepsis plus one or both of
the following ( show table 1 ):
Systemic mean blood pressure is <60 mmHg (or <80 mmHg if the patient has
baseline hypertension) despite adequate fluid resuscitation.
Maintaining the systemic mean blood pressure >60 mmHg (or >80 mmHg if the
patient has baseline hypertension) requires dopamine >5 mcg/kg per min,
norepinephrine <0.25 mcg/kg per min, or epinephrine <0.25 mcg/kg per min
despite adequate fluid resuscitation.
Multiple organ failure — Multiple organ failure refers to the presence of altered
organ function in an acutely ill patient such that homeostasis cannot be maintained
without intervention. The multiple organ dysfunction syndrome (MODS) is classified as
either primary or secondary.
Secondary MODS is organ failure not in direct response to the insult itself, but
as a consequence of a host response (eg, acute respiratory distress syndrome
in patients with pancreatitis). In the context of the definitions of sepsis and
SIRS, MODS represents the more severe end of the spectrum of severity of
illness characterized by SIRS/sepsis.
Although there are no universally applicable criteria for the definition of individual
organ dysfunction in MODS, Marshall critically evaluated the definitions of MODS
adopted in the clinical literature and provided a rationale for the physiologic descriptors
commonly used to define this syndrome [ 6] . Increasing abnormalities in the following
organ-specific parameters correlated with a higher mortality in the ICU:
PO2/FiO2 ratio
Serum creatinine
Platelet count
Glasgow coma score
Serum bilirubin
Pressure-adjusted heart rate, defined by heart rate multiplied by the ratio of
central venous pressure and mean arterial pressure
EPIDEMIOLOGY — In the late 1970s, it was estimated that 164,000 cases of sepsis
occurred in the United States each year [ 7-9] . This has dramatically increased, with
more recent estimates suggesting that more than 650,000 cases of sepsis are
more recent estimates suggesting that more than 650,000 cases of sepsis are
diagnosed annually ( show figure 1 ) [7,10] . Sepsis occurs in approximately 2 percent
of hospitalized patients and up to 75 percent of ICU patients, with a mortality rate of
20 to 50 percent [ 7,11-15] . Despite an 8 percent per year increase in the incidence of
sepsis, hospital case-fatality rates have declined ( show figure 2 ) [7,11,12] .
Mortality rates increase stepwise according to disease severity. In one study, the
mortality rate of SIRS, sepsis, severe sepsis, and septic shock was 7, 16, 20, and 46
percent, respectively [ 16] . Compared to critically ill patients who are not septic,
patients with septic shock remain at an increased risk of death [ 7,17] . A substantial
portion of sepsis cases develop and are managed outside of the ICU [ 18,19] .
Season — The incidence of sepsis is greatest during the winter, which appears
related to the increased likelihood of a respiratory source [ 20] .
Race and ethnicity — It also varies among racial and ethnic groups, with
African-American males at greatest risk ( show figure 3 ) [7] .
Community acquired pneumonia (CAP). Among patients with CAP, severe sepsis
and septic shock will either develop or be present at admission in approximately
48 and 5 percent of patients, respectively [ 28] .
While recognizing that the disease process forms a continuum of severity, clinical trials
have found that definable phases exist on this continuum that characterize populations
at increased risk of morbidity and mortality. As an example, one study evaluated the
natural history of 2527 patients with SIRS [ 16] :
The mortality rate increased progressively along the continuum: 7 percent with
SIRS alone, 16 percent with sepsis, 20 percent with severe sepsis, and 46
percent with septic shock
Clinical trials in the 1980s and 1990s confirmed the prognostic importance of the
definitions of the different sepsis syndromes. Patients with sepsis die at a significantly
lower rate than those with severe sepsis or septic shock on admission or those who
develop shock subsequent to study entry [ 22-25,29] .
Categorical definitions, such as SIRS, severe sepsis, and septic shock, have important
limitations [ 3,30] . They identify patients with a variable baseline or pretreatment risk,
which contributes to the large range in mortality within a category in published trials.
Furthermore, some patients with clinical evidence of sepsis may not fulfill the exact
criteria for a categorical definition such as the sepsis syndrome. These limitations have
led to recognition of the importance of physiologic derangements and individual patient
characteristics in determining the outcome from sepsis [ 3] .
Definitions of sepsis, severe sepsis, and septic shock are based on clinical experience
(ie, "expert" advice) and the correlation of infection progression with appropriate
physiologic responses. However, these criteria may be inadequate for detection of
physiologic responses. However, these criteria may be inadequate for detection of
severe infections in routine daily practice. As an example, the well-established criteria
for SIRS fails to predict outcome among patients who present to the emergency
department with pneumonia [ 28] . In addition, a multicenter study of 1531 patients in
an ICU with infection found that categorizing an infectious process as sepsis or severe
sepsis did not predict prognosis [ 31] . The Surviving Sepsis Campaign Management
Guidelines Committee, the American College of Chest Physicians, and the Society of
Critical Care Medicine Consensus Conference Committee have proposed guidelines to
help identify patients who are at greater risk for sepsis [ 32] .
Underlying disease — The presence of underlying diseases and the functional health
status of the patient are important determinants of outcome in severe sepsis [ 30] .
Risk factors for mortality from sepsis include age above 40 years and comorbid
conditions at the time of diagnosis of sepsis, such as AIDS, hepatic failure, cirrhosis,
cancer, alcohol dependence, and/or immune suppression [ 30,35-38] .
Age — Older patients are at increased risk of severe sepsis, in part because of
comorbid illness and impaired immunologic response to infection [ 7,10,39] .
Malnutrition, increased exposure to potentially resistant bacterial pathogens in nursing
homes, and utilization of medical devices including indwelling catheters and central
venous lines also contribute to this increased risk [ 39] . Older patients are at increased
risk of morbidity and mortality following the development of sepsis [ 7,10] . In the
United States, patients ≥ 65 years of age account for nearly 60 percent of all episodes
of severe sepsis. This percentage is likely to increase over the next 20 years [ 7,10,40]
.
Site of infection — The site of infection in patients with sepsis may be an important
determinant of outcome, with urosepsis being associated with lower mortality rates
[30,41] . One study, for example, found mortality rates from sepsis between 50 and 55
percent when the source of infection was unknown or was gastrointestinal or
pulmonary; in comparison, the mortality rate was only 30 percent when the source
was the urinary tract [ 41] .
LONG-TERM SURVIVAL — Prospective studies indicate that most patients who die
following sepsis do so within the first six months [ 45,46] . In other words, mortality
tends to stabilize after six months according to the survival curves of patients with
sepsis (blood culture positive).
REFERENCES
GRAPHICS
Definitions of systemic inflammatory response syndrome (SIRS)
and different degrees of severity of sepsis
Condition Description
Two or more of the following conditions: temperature >38.5°C
Systemic
or <35.0°C; heart rate of >90 beats/min; respiratory rate of
inflammatory
>20 breaths/min or PaCO 2 of <32 mm Hg; and WBC count of
response
>12,000 cells/mL, <4000 cells/mL, or >10 percent immature
syndrome
(band) forms
Points represent the annual incidence rate, and I bars the standard error.
Data from: Martin, GS, Mannino, DM, Eaton, S, Moss, M. The epidemiology of
sepsis in the United States from 1979 through 2000. N Engl Med 2003;
348:1546.
Overall in-hospital mortality rate among patients
hospitalized for sepsis, 1979-2000
Mortality averaged 28 percent during the first six years of the study
and 18 percent during the last six years. The I bar represent the
standard error. Data from: Martin, GS, Mannino, DM, Eaton, S, Moss, M.
The epidemiology of sepsis in the United States from 1979 through
2000. N Engl Med 2003; 348:1546.
Population-adjusted incidence of sepsis, according to race, 1979 -
2000
Points represent the annual incidence rate, and I bars the standard error.
Data from: Martin, GS, Mannino, DM, Eaton, S, Moss, M. The epidemiology of
sepsis in the United States from 1979 through 2000. N Engl Med 2003;
348:1546.
Number of cases of sepsis in the United States, according to
causative organism, 1979 - 2000
Points represent the number of cases for the given year, and I bars the
standard error. Data from: Martin, GS, Mannino, DM, Eaton, S, Moss, M. The
epidemiology of sepsis in the United States from 1979 through 2000. N Engl
Med 2003; 348:1546.
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